ABSTRACT
Ischemia/reperfusion injury in renal transplantation leads to slow or initial nonfunction, and predisposes to acute and chronic rejection. In fact, severe ischemia reperfusion injury can significantly reduce graft survival, even with modern immunosuppressive agents. One of the mechanisms by which ischemia/reperfusion causes injury is activation of endothelial cells resulting in inflammation. Although several therapies can be used to prevent leukocyte recruitment to ischemic vessels (e.g. antiadhesion molecule antibodies), there have been no clinical treatments reported that can prevent initial immediate neutrophil recruitment upon reperfusion. Using intravital microscopy, we describe abrogation of immediate neutrophil recruitment to ischemic microvessels by the K(ATP) antagonist glibenclamide (Glyburide). Further, we show that glibenclamide can reduce leukocyte recruitment in vitro under physiologic flow conditions. ATP-regulated potassium channels (K(ATP)) are important in the control of cell membrane polarization. Here we describe profound hyperpolarization of endothelial cells during hypoxia, and the reduction of this hyperpolarization using glibenclamide. These findings suggest that control of endothelial membrane potential during ischemia may be an important therapeutic tool in avoiding ischemia/reperfusion injury, and therefore, enhancing transplant long-term function.
Subject(s)
Endothelium, Vascular/physiology , Hypoxia/physiopathology , KATP Channels/antagonists & inhibitors , Leukocytes/physiology , Reperfusion Injury/prevention & control , Animals , Cats , Cell Membrane/physiology , Endothelium, Vascular/drug effects , Gelatin/pharmacology , Glyburide/pharmacology , Humans , Hypoxia/chemically induced , Neutrophils/physiology , Pinacidil/pharmacology , Umbilical Veins/drug effects , Umbilical Veins/physiologyABSTRACT
Tourniquets are widely employed in orthopaedic practice to maintain a bloodless operative field during extremity surgery. In areas of the world where reliable pressurized air systems for tourniquet inflation are not available, and as an alternative to the traditional Esmarch bandage, we report on the successful and safe use of a novel hand-held, battery-operated limb tourniquet.
Subject(s)
Lower Extremity/surgery , Orthopedic Procedures/instrumentation , Tourniquets , Upper Extremity/surgery , Adolescent , Adult , Aged , Air Pressure , Equipment Design , Humans , Lower Extremity/blood supply , Male , Middle Aged , Orthopedic Procedures/adverse effects , Upper Extremity/blood supplyABSTRACT
The Bedford Orthopaedic Centre is situated in Umtata at the heart of the former homeland of the Transkei in the Eastern Cape of South Africa. It acts as an orthopaedic and trauma referral hospital for a mainly rural population approaching 4 million. This article focuses on the workload of the hospital over a 4-month period and like many hospitals in South Africa we highlight the difficulties it faces with the trauma epidemic.
Subject(s)
Orthopedics/organization & administration , Workload , Wounds and Injuries/surgery , Accidents, Traffic/statistics & numerical data , Adolescent , Adult , Aged , Aged, 80 and over , Fractures, Bone/epidemiology , Fractures, Bone/etiology , Fractures, Bone/surgery , Humans , Male , Middle Aged , Prospective Studies , Referral and Consultation , South Africa/epidemiology , Trauma Centers/organization & administration , Violence/statistics & numerical data , Wounds and Injuries/epidemiology , Wounds and Injuries/etiologyABSTRACT
Formula-fed babies contract gastroenteritis more than breast-fed babies, which is of concern to mothers who cannot breastfeed or, as with HIV-infected mothers, are discouraged from breastfeeding. The ability of endogenous breastmilk xanthine oxidase to generate the antimicrobial radical nitric oxide has been measured and its influence on the growth of Escherichia coli and Salmonella enteritides examined. Breastmilk, but not formula feed, generated nitric oxide. Xanthine oxidase activity substantially inhibited the growth of both bacteria. An important natural antibiotic system is missing in formula feeds; the addition of xanthine oxidase may improve formula for use when breastfeeding is not a safe option.
Subject(s)
Anti-Bacterial Agents/pharmacology , Milk, Human/enzymology , Xanthine Oxidase/pharmacology , Anti-Bacterial Agents/isolation & purification , Drug Interactions , Escherichia coli/drug effects , Escherichia coli/growth & development , Female , Humans , Hydrogen Peroxide/pharmacology , Hypoxanthine/pharmacology , Milk, Human/metabolism , Nitric Oxide/biosynthesis , Salmonella enteritidis/drug effects , Salmonella enteritidis/growth & development , Xanthine Oxidase/isolation & purification , Xanthine Oxidase/metabolismABSTRACT
Xanthine oxidoreductase (XOR) catalyses the reduction of the therapeutic organic nitrate, nitroglycerin (glyceryl trinitrate, GTN), as well as inorganic nitrate and nitrite, to nitric oxide (NO) under hypoxic conditions in the presence of NADH. Generation of nitric oxide is not detectable under normoxic conditions and is inhibited by the molybdenum site-specific inhibitors, oxypurinol and (-)BOF 4272. These enzymic reactions provide a mechanism for generation of NO under hypoxic conditions where nitric oxide synthase does not function, suggesting a vasodilatory role in ischaemia.
